"Abstract: Chronic Fatigue Syndrome (CFS) is distinguished by a persistent malaise and lethargy that physical or mental exertion exacerbates for a period of several days. Sufferers can identify a clear-cut beginning to their condition. In many, it follows a viral infection such as glandular fever. Sufferers also experience cognitive difficulties and, sometimes, autonomic disturbances such as dizziness on standing, gastrointestinal upsets, cardiovascular irregularities and immune system dysfunction."

As well as voxel-based morphometry, a novel voxel-based quantitative analysis of T1 - and T2 -weighted spin-echo (T1w and T2w) MRI signal level was performed. Severity scores included the Bell CFS disability scale and scores based on the 10 most common CFS symptoms. Hospital Anxiety and Depression Scale (HADS) depression and anxiety scores were included as nuisance covariates.

By relaxing the threshold for cluster formation, we showed that the T1w signal is elevated with increasing CFS severity in the ventrolateral thalamus, internal capsule and prefrontal WM.

Earlier reports of WM volume losses and neuroinflammation in the midbrain, together with the upregulated prefrontal myelination suggested here, are consistent with the midbrain changes being associated with impaired nerve conduction which stimulates a plastic response on the cortical side of the thalamic relay in the same circuits.

The T2w signal versus CFS duration and comparison of T2w signal in the CFS group with the NC group revealed changes in the right middle temporal lobe WM, where impaired communication can affect cognitive function.

Adjustment for depression markedly strengthened cluster statistics and increased cluster size in both T1w severity regressions, but adjustment for anxiety less so. Thus, depression and anxiety are statistical confounders here, meaning that they contribute variance to the T1w signal in prefrontal WM but this does not correlate with the co-located variance from CFS severity.

MRI regressions with depression itself only detected associations with WM volume, also located in prefrontal WM. We propose that impaired reciprocal brain-body and brain-brain communication through the midbrain provokes peripheral and central responses which contribute to CFS symptoms.

Although anxiety, depression and CFS may share biological features, the present evidence indicates that CFS is a distinct disorder.

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This looks really interesting. I wonder what it all means. I think it suggests that we have the opposite of MS - too much myelination (is "nerve insulation" a fair description?) is disrupting brain signal processing.

The full text is available for free, for folks able to understand this stuff.

Yes, my MRI shows "several punctate subcortical T2 hyperintensities" ("bright spots"), but since no one knows what they mean, they apparently mean nothing. It would be interesting to have it reviewed by someone like Dr Barnden.

Ditto. Punctate white-matter lesions. My docs admitted they didn't know what it was, but they did not act unworried. Two separate reports stated in almost identical language what amounted to "looks kind-of sort-of like migraine damage." Neither report was exchanged (i.e. Doctor 1 didn't see Doctor 2's report, and vice-versa). I said to Doctor 1, "this language is equivocal. You say 'may be' migraine, but that's just the closest thing to what you're looking at, right? It looks kind of like migraine, but not really?"

He was a pretty honest guy, and after a minute, he nodded. "Yes, it's almost like that but not quite." He signed me up to run an MRI for 6 mo. later, but given he didn't know what it was, I think it was a try for peace of mind. If they hadn't increased in number or grown any larger, he could say, "we don't know what it is -- but at least it's not progressing."

@jimells , we seem to be exchanging a lot of these sorts of stories, lately.

1) The researchers used voxel-based regressions. This is a very subtle, sensitive way of gauging differences in brain anatomy using scans + statistics. Read the introduction in this Wikipedia article for more.

2) In addition to voxel-based morphometry, they did T1 and T2-weighed spin echoes.

T1w shows changes in levels of myelin.

T2w shows blood volume in that region

3) They used 25 subjects who met BOTH Fukuda and CCC definitions, ages 19-47. They discontinued meds for the purposes of the study. Those who were too ill to stop their meds were excluded. Therefore it's viable to assume that, like the vast majority of ME/CFS studies, this one only ended up testing people who have minor-moderate form of the illness.

Study period was delayed if the patient was too ill to get the scan, and then resumed once they were well enough to continue -- I think that's good practice, really, or you could lose a lot of subjects in a patient pop like this.

There were 25 age-, gender- and even weight-matched, non-related controls. They were not on meds and had no major illnesses.

4) Three CFS severity scores were used:

Bell's CFS disability scale

Somatic Symptom Score

Fatigue

Change in sleep pattern

Dizziness on standing

Muscle pain

stomach symptoms

overall level of function

Neurological Symptom Score

change in concentration

change in short-term memory

headaches

emotional swings

(For these, low scores = higher severity)

They also carried out a Hospital Anxiety and Depression Scale (HADS) questionnaire.

5) @duncan , these MR images were acquired on a Philips 1.5-T scanner.

There was no correlation between CFS disability and anxiety, or somatic symptoms and anxiety.

8) Nerve conduction through the midbrain appears to be impaired in CFS. This was shown through an increase in prefrontal myelination (via T1w) in sickest patients, and volume loss in midbrain white matter (via T2w).

9) CFS severity effects are not directly related to depression or anxiety (even though depression is correlated, it's not causative.) Anxiety and depression were included as 'nuisance' covariates in order to remove any apparent contribution to severity correlations.

If this appeared to weaken the correlation of damage to that part of the brain with CFS severity, one could feel more confident in saying that depression is at least a strong part of what drives CFS symptom severity; that is, it is a somatoform disorder.

Instead, both T1w imaging and T2w imaging with depression and anxiety 'removed' from the picture showed a stronger correlation to CFS severity rather than a weaker one. In other words, if you removed the 'white noise' caused by depression/anxiety, it strengthened the association between brain abnormalities and CFS severity.

Thus,

...depression is a statistical 'confounder'... Adjusting out the depression-related variance... results in a stronger statistical inference.... All MRI regressions with depression itself yielded only one cluster which was located in the same prefrontal WM in which the depression-independent T1w versus CFS severity regression was detected. That is, MRI signals in no other brain locations (which might influence CFS severity) correlated with depression, and therefore a depression-driven hypothesis for CFS was not supported here.

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10) Volume loss might be due to astrocyte shrinkage; it's definitely not due to oligodendrocytes.

Overall conclusions:

Elevation of myelination is severity-dependent. There are midbrain nerve conduction issues in CFS, as defined by CCC, with midbrain volume loss and midbrain neuroinflammation. This might help explain autonomic and cognitive issues experienced by PWME. Despite the fact that severity of the illness correlates to depression, the neuroimaging studies don't support that CFS is caused by depression; in fact, when depression is eliminated as a 'possibility', the correlation between midbrain damage and CFS severity increases rather than disappears. CFS is therefore a distinct disorder rather than a form of depression.

Guys, please read this study for yourself. I am an absolute novice at both statistics and MRI, and, er...

If one technology uncovers footprints, shouldn't someone try to complement the effort with other technologies to generate a comprehensive image of what is going on in our brains?

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There have been a number of studies that use various brain imaging techniques. Unfortunately they have all been small numbers of patients and the results have been buried under the noise generated by the PACE propaganda machine.

I was in a US govt sponsored study. I demonstrated neurological symptoms. They found subtle abnormalities with a 1.5 philips. Another group with a 3.0 found several not-so-subtle problems. I pushed the original group for a 3.0 AND a PET AND a SPECT - and was turned down for all three. Not part of the protocol, I was told.

My response was if you are interested in discerning neurological abnormalities, then start walking the walk and cough up the money and LOOK.